Glucocorticoids are used clinically for topical therapy of most cutaneous diseases, at a cost of tens of millions of dollars annually. The mechanism of action of these compounds has been studied extensively in other tissues. This involves entry into the cell, binding to a cytoplasmic receptor, and movement of the receptor-steroid complex into the nucleus, where it binds to an acceptor. New messenger ribonucleic acid is formed, and this causes the glucocorticoid-induced changes in the activities of the cell. The proposed research will examine the mechanism of glucocorticoid action in human skin, both in the epidermis and the dermis, in normal and diseased skin. The various steps in the pathway of glucocorticoid interaction with the cells will be compared in the skin of patients with diseases such as psoriasis, and the molecular basis of the resistance of such lesions in some patients will be examined.